Type I interferons (IFNα/β) constitute a family of secreted proteins with pleiotropic cellular effects including inhibition of cell proliferation, induction of differentiation, modulation of the immune system and alterations of the cell surface. These activities have promoted their use in the clinic mainly in malignant and viral diseases. Interferon alpha (IFNα) has been used in the clinic for haematological malignancies, solid tumours and viral syndromes. Unfortunately, their use as anti-cancer drugs have shown only limited success, and in situations where they display clinical benefit their mechanism of action remains unclear (Grander and Einhorn, 1998, Acta Oncol., 37, 331-338). Overall, IFNα has only limited activity on neoplams and severe cancers are resistant to the anti-proliferative action induced by Type I interferons.
Recent experimental models (Reya et al., 2001, Nature, 414, 105-111; Polyak and Hahn, 2006, Nature Med.; 11: 296-300) support the hypothesis that many cancers are driven by a small number of so called “cancer stem cells” (CSCs). These CSCs are presumed to be resistant to classical anti-proliferative chemotherapy drugs. Despite the fact that the tumour mass is reduced by the chemotherapy that eliminates dividing cells, the frequently observed re-occurrence of the disease is caused by new tumour cells generated by chemotherapy-resistant, and thus surviving CSCs. One of the reasons CSCs are thought to be resistant to chemotherapy is their general quiescence, which is also known as dormancy Therefore, there is a clear need in the art for novel approaches towards treating and managing cancers, especially those showing resistance to classical anti-proliferative chemotherapy drugs such as stem cell driven cancers (Polyak and Hahn, 2006, above).